Bowel disorders (BDs) are a spectrum of chronic gastrointestinal (GI) disorders, characterized by abdominal pain, discomfort, bloating, distension, and bowel habit abnormalities. According to Rome V classification, BDs are classified into six categories: (1) irritable bowel syndrome (IBS); (2) chronic constipation (CC); (3) functional diarrhea (FDr); (4) functional abdominal bloating (FAB); (5) unclassified BD (U-BD); and (6) opioid-induced constipation (OIC). OIC is distinct from other BDs due to its specific pharmacological etiology but often overlaps with IBS and FC, warranting inclusion in this classification framework.
IBS is defined by recurrent abdominal pain and/or discomfort associated with changes in bowel habits (constipation, diarrhea, or a mix of constipation and diarrhea) with symptom onset at least 6 months prior to diagnosis and symptoms present during the preceding 3 months.
The recent Rome Foundation Global Epidemiological Study (RFGES) found that approximately 33% of participants completing an internet survey met criteria for at least one BD. The global prevalence of IBS was 4.3% across 24 countries surveyed online, with higher rates in Western Europe compared with Asia. The prevalence peaked at 5% among individuals aged 18-39 years and showed a 1.8:1 women-to-men ratio. Subtype distribution was similar except for IBS-U, which had a lower prevalence. IBS significantly affects quality of life and productivity with the greatest burden due to IBS-D and IBS-C.
Recurrent, but not continuous, abdominal pain or discomfort on average at least three days per month in the last 3 months, associated with two or more of the following criteria: (1) Related to defecation; (2) Associated with a change in frequency of stool; (3) Associated with a change in form (appearance) of stool. Criteria symptom onset at least six months prior to diagnosis. Supportive criteria: abdominal pain/discomfort should not be only related to menses.
Notable changes from Rome IV include: (1) Abdominal discomfort has been added to the diagnostic criteria for IBS; (2) Abdominal pain or discomfort should be present at least 3 days per month on average during the preceding 3 months; (3) The new specification that abdominal pain or discomfort should not be continuous has been added to differentiate IBS from centrally mediated abdominal pain syndrome; (4) A supportive criterion has been added indicating that abdominal pain or discomfort should not be only related to menses to differentiate IBS from menstrual-related symptoms.
With the implementation of Rome IV, the reported prevalence of IBS decreased significantly compared with Rome III. The RFGES found the reason for this decline was primarily due to the higher frequency threshold for pain in Rome IV (i.e., at least one day/week) vs Rome III (i.e., at least 2-3 days/month), and to a lesser extent to the removal of "discomfort". Several studies have reported IBS patients who experience abdominal discomfort without pain, particularly in some countries. To address these limitations, Rome V reintroduced "discomfort" and lowered the frequency threshold for abdominal pain or discomfort to ≥3 days per month.
IBS continues to be classified into four main subtypes based on the predominant bowel habit, as determined by the Bristol Stool Form Scale (BSFS): IBS with constipation (IBS-C), with diarrhea (IBS-D), with mixed bowel habit (IBS-M), or with unclassified bowel habit (IBS-U).
For clinical trials, subtyping based on at least 2 weeks of daily diary data is recommended using the "25%-rule". Subtype categories are considered mutually exclusive.
Clinicians should make a positive diagnosis of IBS based on symptoms, emphasizing that IBS is not a diagnosis of exclusion. In most patients, when IBS diagnostic criteria are fulfilled and alarm features are absent, testing should be selective and limited. The predictive value of alarm features for identifying organic disease that might explain IBS symptoms is modest. However, this limited performance may partially reflect the imprecise characterization of certain alarm features, for example, distinguishing nocturnal symptoms that awaken the patient from those that merely affect sleep quality.
Since certain organic conditions (e.g., inflammatory bowel disease [IBD], celiac disease, microscopic colitis) can mimic IBS, limited targeted testing may be appropriate. When considering such tests, clinicians should weigh the pre-test probability of these conditions, guided by their prevalence in symptomatic patients. Routine follow-up visits with targeted investigations for those with persistent symptoms is cost-effective and often more reassuring than an exclusionary diagnostic approach. Notably, negative test results do not necessarily improve reassurance or quality of life, particularly in young patients with IBS.
Initial serologic laboratory testing and stool testing for inflammation in patients with suspected IBS: A systematic review and meta-analysis found that a C-reactive protein (CRP) <0.5 mg/dl was associated with a <1% probability of IBD, while erythrocyte sedimentation rate (ESR) and fecal lactoferrin had little value in differentiating IBS from IBD. Another meta-analysis reported that fecal calprotectin of ≤50 μg/g had a 99.8% negative predictive value but only a 9% positive predictive value in differentiating between IBS and IBD. Because of the high negative predictive value, fecal calprotectin is widely used to exclude IBD in patients with chronic diarrhea, though it lacks specificity and may be elevated in older individuals, obesity, infection, or with proton pump inhibitors (PPIs) or non-steroidal anti-inflammatory drugs (NSAIDs) use.
A 2017 meta-analysis of 36 studies found the prevalence of biopsy-confirmed celiac disease in IBS to be 3.3%. Higher rates have been reported in Middle Eastern and Asian countries. Most IBS clinical guidelines recommend serologic testing for celiac disease using IgA anti-tTG and a quantitative serum IgA level to exclude selective IgA deficiency. Notably, the sensitivity of anti-tTG is reduced in patients adhering to a gluten-free diet.
Other stool laboratory testing: Stool analysis for bacteria, ova, and parasites may be appropriate in patients with diarrhea who live in or have recently traveled to areas where infectious diarrhea is common. However, in areas with a low incidence of infectious diarrhea the diagnostic yield of stool testing is low. Most clinical guidelines do not recommend routine stool testing for bacterial or viral pathogens in patients with chronic IBS-like symptoms. Nevertheless, Giardia lamblia, the most common parasite causing chronic diarrhea in adults worldwide, should be considered.
Fecal hemoglobin tests (FOBT, FIT, multi-target stool DNA) are appropriate for colorectal cancer screening but are not recommended for differentiating IBS from structural GI disease. Similarly, routine fecal elastase testing is not recommended. Although an early study reported a higher prevalence of exocrine pancreatic insufficiency among IBS patients, a subsequent study did not confirm this association, identifying only a small number of cases, mostly in patients with a history of alcohol use.
Bile Acid Malabsorption (BAM): Although testing for BAM is not recommended in the initial IBS evaluation, it should be considered, when available, in patients with chronic diarrhea who do not respond to standard treatment. The SeHCAT retention test is considered the gold standard test for BAM but is not available in many countries. A more accessible alternative is the serum 7α-hydroxy-4-cholesten-3-one (7C4) blood assay, which is a marker of hepatic bile acid synthesis; however, its utility in the evaluation of IBS-D has not been rigorously evaluated.
Carbohydrate maldigestion: Carbohydrate (e.g., lactose, fructose, sorbitol, sucrose, starch) maldigestion can cause diarrhea, cramping and bloating. Lactose maldigestion is most common, affecting approximately two-thirds of the global adult population, with marked ethnic and geographical variation. In one study of IBS patients, 35% had lactose maldigestion, 64% fructose maldigestion, and 25% both — rates similar to the general population. Lactose hydrogen breath testing may be clinically useful in select patients, though routine testing for lactose maldigestion is not recommended as part of the initial IBS evaluation.
Sucrase-isomaltase deficiency (SID) is increasingly recognized as a potential cause of IBS-like symptoms. The gold standard for diagnosing SID is quantitative disaccharidase activity assay testing of duodenal biopsies, which requires special handling and referral to a reference laboratory. The prevalence of SID in IBS remains uncertain, and the Rome V committee does not recommend routine testing at this time.
Small intestine bacterial (SIBO) or intestinal methanogen overgrowth (IMO): Dysfunctional microbiota has been implicated in the pathogenesis of IBS symptoms in several studies. SIBO appears more frequently associated with IBS with diarrhea, whereas IMO is more often linked to IBS-C.
IBS is a multifactorial disorder that is best conceptualized within a biopsychosocial model, with genetic, environmental, and psychosocial factors influencing susceptibility and symptom expression. Common triggers for IBS onset or flares include gastroenteritis, dietary factors, psychological factors, chronic stress, and surgeries. Over 10% of patients develop post-infection IBS (PI-IBS) after an acute gastroenteritis and recent data suggest IBS may also follow COVID-19. A history of childhood or adulthood abuse increases the risk of IBS by nearly 3-fold and adult stressors can contribute to both onset and persistence.
The pathophysiologic mechanisms of IBS include altered GI motility, visceral hypersensitivity, altered intestinal permeability, immune activation, altered gut microbiota, and abnormal gut-brain signaling. GI transit may be accelerated or delayed, and visceral hypersensitivity can result from peripheral sensitization and/or a central amplification. Autonomic nervous system tone and hypothalamic-pituitary-adrenal axis abnormalities have been described, but their roles remain under investigation. Immune activation may also contribute to IBS symptoms, supported by evidence from PI-IBS models, mast cell mediated pathways, and local immune responses to food antigens. Serotonin likely plays a modulatory role, with subtype-specific alterations reported, though measurement challenges remain. Finally, abnormal intestinal permeability, particularly in IBS-D and PI-IBS, occurs in 4%-62% of patients.
Microbiota studies in IBS have revealed alterations in both microbial composition and metabolic function, with metagenomic and metabolomics studies suggesting IBS subtype- and symptom-specific responses. Food-related symptoms may result from exaggerated sensory and motor responses, altered colonic fermentation, abnormal gas handling, or microbial instability. While food allergies are rare, local allergy-like intestinal reactions have been demonstrated using confocal laser endomicroscopy, and IgG immunoreactivity to foods such as wheat and milk has been implicated. BAM has been estimated to be present in 25% of patients with IBS-D. In addition, alterations in short chain fatty acids (SCFA), key microbial metabolites influencing motility, permeability, secretion, and immune responses have also been proposed as contributing factors in IBS pathophysiology.
Key steps of the management of BDs are outlined in Figure 5. A strong patient–provider relationship is central to effective IBS management, as it is associated with improved symptom control, greater treatment adherence and reduced healthcare utilization. Clinicians should identify each patient's most bothersome symptoms to personalize treatment goals and guide shared decision-making.
A systematic review found exercise modestly improved global IBS symptoms compared with usual care, though the certainty of evidence was very low due to potential bias and the small sample size. Fiber supplementation is safe, relatively inexpensive, and potentially beneficial; a meta-analysis of 14 trials found benefit with soluble (psyllium/ispaghula husk, RR=0.83 NNT=7) whereas insoluble (bran) fiber did not (RR=0.90). Among dietary interventions for IBS, a network meta-analysis found the strongest evidence for a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet. The British Dietetic Association/NICE diet was also more effective than a habitual diet for improving global symptoms. Emerging dietary interventions that also show promise include the Mediterranean diet, a starch-reduced and sucrose-reduced diet, a FODMAP-simple diet, and a gluten-free diet.
Constipation Predominant Symptoms:
Laxatives: Polyethylene glycol (PEG; 13.8-41.4 grams/day) has not been extensively studied in IBS-C but is commonly recommended as initial treatment given its proven efficacy in relieving constipation. In a single 4-week randomized controlled trial (RCT) in adults with IBS-C, PEG significantly improved stool frequency, stool consistency, and straining, but did not improve abdominal pain or bloating.
Secretagogues: Current pharmacologic therapies for IBS-C include secretagogues and ion transport inhibitors, which enhance intestinal fluid secretion through distinct mechanisms. Lubiprostone activates type-2 chloride channels (ClC-2), while linaclotide and plecanatide activate guanylate cyclase C receptors (GC-C) resulting in an increase in chloride secretion into the GI lumen.
In phase III trials, lubiprostone (8 μg twice daily, 12-week trials) produced higher overall response rates (moderate or significant relief of IBS ≥2 of the first 4 weeks and ≥6 of the total 12 weeks treatment period) than placebo (17.9% versus 10.1%), with nausea (8% versus 4% placebo) and diarrhea (6% versus 4% placebo) as the most common adverse events (AEs).
Linaclotide (290 μg once daily, 12- and 26-week trials) significantly increased the proportion of patients reporting 'considerable' or 'complete' relief of their IBS-C symptoms for at least 6 of the first 12 weeks than patients receiving placebo. Benefits for stool frequency occur relatively rapidly while the maximal benefits for abdominal pain or bloating occur at 6-8 weeks. Diarrhea was the most frequent AE (18%-20% vs. 2% placebo).
In the Phase III trials, plecanatide (3 mg once daily, 12-week trials) significantly improved the composite endpoint (≥30% improvement in abdominal pain and an increase ≥1 complete spontaneous bowel movements [CSBM] per week from baseline) vs. placebo (27.4% vs. 16.9%). Like linaclotide, stool frequency tends to occur sooner than benefits for abdominal pain or bloating. Diarrhea occurred in 4-5% vs. 1% with placebo.
NHE3 Inhibitor: In contrast to secretagogues, tenapanor decreases the absorption of sodium by inhibiting the intestinal sodium/hydrogen exchanger isoform 3 (NHE3). Tenapanor (50 mg twice daily, 12- and 26-week trials) significantly improved the composite endpoint compared with placebo (27.0% vs 18.7%; 36.5% vs 23.7%, respectively) with diarrhea as the most common AE (16% vs. 3.7%).
Prokinetic Agents (5-HT4 receptor agonists): Tegaserod improved IBS-C symptoms in phase III trials; however, it is no longer available for commercial reasons. Only a limited number of phase II trials have been conducted with mosapride and prucalopride has not been widely evaluated in patients with IBS-C.
Diarrhea Predominant Symptoms:
Bile Acid Sequestrants: Two small open label studies have shown that colestipol and colesevelam may improve bowel symptoms in patients with IBS-D, although no comparators were provided and no head-to-head comparison data is available.
Opioid Agonists/Antagonists: Loperamide is a synthetic peripheral mu-opioid receptor agonist that decreases colonic transit and increases water and ion absorption. Some clinical guidelines recommend loperamide as initial treatment for IBS-D, particularly for control of stool frequency and urgency.
Eluxadoline is a mixed μ- and κ opioid receptor agonist and a δ opioid receptor antagonist. In phase III trials, IBS-D patients receiving eluxadoline (75 or 100 mg twice daily) for either 26 or 52 weeks were more likely to meet the primary composite endpoint than patients randomized to placebo (23.9% and 25.1% vs. 17.1%, respectively for the 26-week study; 28.9% and 29.6% vs. 16.2%, respectively for the 52-week study). The most common AEs reported with eluxadoline (combined doses) vs placebo were nausea (7.7% vs. 5.1%), constipation (8.0% vs. 2.5%), and abdominal pain (6.5% vs 4.1%). Due to serious AEs, eluxadoline should not be prescribed for patients with a history of pancreatitis, sphincter of Oddi dysfunction, alcohol abuse or prior cholecystectomy and in severe hepatic impairment.
Pain Predominant Symptoms:
Antispasmodics and peppermint oil: Antispasmodic agents reduce smooth intestinal muscle contractility through direct myorelaxant effects or antimuscarinic or anticholinergic activity. Peppermint oil acts primarily via calcium channel blockade, producing direct smooth muscle relaxation. A meta-analysis of 22 randomized, placebo-controlled trials found that, among the various antispasmodics studied, otilonium, hyoscine, and peppermint oil showed the most consistent efficacy. Other meta-analyses have reported a NNT between 3 and 4 for peppermint oil compared with placebo. In addition, antispasmodic combinations, like alverine citrate and pinaverium bromide combined with simethicone, have shown to improve abdominal pain and bloating in controlled studies. Common side effects with traditional antispasmodics include dry mouth, constipation, urinary retention,